the energy study: evaluation of safety and tolerability of inz-701 in infants with enpp1 deficiency or abcc6 deficiency

Conditions: Ectonucleotide Pyrophosphatase/phosphodiesterase1 Deficiency; Autosomal Recessive Hypophosphatemic Rickets; Generalized Arterial Calcification of Infancy; ATP-Binding Cassette Subfamily C Member 6 Deficiency; Pseudoxanthoma Elasticum

Summary: the primary purpose of study inz701-104 (the energy study) is to assess the safety and tolerability of inz-701 in infants with enpp1 deficiency or with abcc6 deficiency.

inz-701 is an ectonucleotide pyrophosphatase/phosphodiesterase 1 (enpp1) enzyme replacement therapy in development for the treatment of the ultra-rare genetic disorder, enpp1 deficiency or with abcc6 deficiency. study inz701-104 (the energy study) is a phase 1b, open-label study to assess the safety, tolerability, pharmacokinetics (pk), and pharmacodynamics (pd) of inz-701 in infant study participants with enpp1 deficiency or abcc6 deficiency. the study will consist of up to a 60-day screening period, a 52-week treatment period during which study participants will receive inz-701, an extension period during which participants may continue to receive inz-701 until it is commercially available in the country where the participant resides, or until an alternative study of inz-701 is available, and an end of treatment (eot) visit 30 days after the last dose of inz-701. upon treatment discontinuation, participants will continue to be followed for their ongoing disposition for survival outcome at least quarterly through the end of the study.

Eligibility criteria:
inclusion criteria: 1. caregiver(s) must provide written or electronic consent after the nature of the study has been explained, and prior to any research-related procedures, per international council for harmonisation (ich) good clinical practice (gcp) 2. study participant must have a confirmed post-natal molecular genetic diagnosis of enpp1 deficiency or abcc6 deficiency with biallelic mutations (ie, homozygous or compound heterozygous) performed by a college of american pathologists/clinical laboratory improvement amendments (cap/clia) certified laboratory 3. study participants must have clinical manifestations of gaci or gaci-2, which may include, but are not limited to, pathologic ectopic calcification, heart failure, respiratory distress, edema, cyanosis, hypertension, and cardiomegaly 4. study participant must be male or female from birth to \<1 year of age at baseline (day 1) 5. study participant must weigh ≥0.5 kg at the time of the first dose of inz-701 in this study 6. in the opinion of the investigator, the study participant must be able to complete all aspects of the study 7. study participant's caregiver(s) must agree to provide access to their child's relevant medical records exclusion criteria: 1. in the opinion of the investigator, presence of any clinically significant disease or laboratory abnormality (outside of those considered associated with the diagnosis of enpp1 deficiency or abcc6 deficiency) that precludes study participation or may confound interpretation of study results, including known uncontrolled thyroid disease or unrelated connective tissue, bone, mineral, or muscle disease 2. care has been withdrawn or study participant is receiving end of life care or hospice only 3. known malignancy 4. known intolerance to inz-701 or any of its excipients 5. concurrent participation in another non-inozyme interventional study 6. receipt of any non-inozyme investigational new drug within 5 half-lives of the last dose of the other investigational product or within 4 weeks prior to the first dose of inz-701, whichever is longer, or use of an investigational device, through completion of participation in the study

Keywords: ectonucleotide pyrophosphatase/phosphodiesterase1 deficiency hypopyrophosphatemia enpp1 generalized arterial calcification of infancy gaci autosomal recessive hypophosphatemic rickets type 2 arhr2 atp-binding cassette subfamily c member 6 deficiency abcc6 pseudoxanthoma elasticum pxe